Effects of diets on risks of cancer and the mediating role of metabolites

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.


Supplementary Figures
Figure S1.Associations between diet components of MEDAS and MIND and overall cancer risk (N=187,485).

Figure S2 .
Figure S2.Associations between MEDAS and MIND scores and overall cancer risk stratified by basic characteristics (N=187,485).

Figure S3 .
Figure S3.Associations between MEDAS and MIND scores and 22 specific types of cancer risk stratified by basic characteristics Figure S4.Selection of metabolites in in training set (N=121,382).

Figure S6 .
Figure S6.Flowchart of the study

Figure S1 .
Figure S1.Associations between diet components of MEDAS and MIND and overall cancer risk (N=187,485) HR: hazard ratio; CI: confidence interval.The HR and 95%CI were estimated using Cox regression with adjustment for covariates in model 3 (two-sided Wald test).The gray dashed line represents the null (HR = 1).Each point shows the point estimate of HR from cox regression.Bars show 95%CI.Diet components of these two scores were treated as continuous in the model.Source data are provided with this publication as a Source Data file.

Figure S2 .
Figure S2.Associations between MEDAS and MIND scores and overall cancer risk stratified by basic characteristics (N=187,485) BMI body mass index; HR: hazard ratio; CI: confidence interval; MEDAS: mediterranean diet adherence screener; MIND: Mediterranean-DASH Diet Intervention for Neurodegenerative Delay.The HR and 95%CI were estimated using Cox regression, adjusting for covariates in model 3, and including the cross-product term of MEDAS (or MIND) and the basic characteristics in multivariable regressions (two-sided Wald test).The gray dashed line represents the null (HR = 1).Each blue point shows the point estimate of HR from cox regression.Bars show 95%CI.Source data are provided with this publication as a Source Data file

Nleukemia=161513.
Figure S4.Selection of metabolites in in training set (N=121,382).ENM: elastic net model.(a-d) 10-fold cross-validation ENM Cox regression models with α value of 0.25, 0.50, 0.75, and 1.00 were used to select metabolites.Metabolites with coefficients not equal to zero were selected.(e) Venn plot was used to visually display the shared metabolites with α values of 0.5, 0.75, and 1 in ENM (f) The Y-axis represents the shared metabolites with α values of 0.5, 0.75, and 1 in ENM, while the

Figure S5 .
Figure S5.Associations between the MEDAS and MIND scores, metabolites, and overall cancer risk (N=85,669) (a-b) SE: standard error.Multivariable linear regression was used to obtain the β coefficient and SE of the metabolites (two-sided Wald test).The Y-axis represents the metabolites, while the X-axis represents β coefficient of these metabolites.The point size represents the SE of these metabolites, the point color represents the p-value.(c) HR: hazard ratio; CI: confidence interval; MEDAS: mediterranean diet adherence screener; MIND: Mediterranean-DASH Diet Intervention for Neurodegenerative Delay.The HR and 95%CI were estimated using Cox regression with adjustment for covariates in model 3 (two-sided Wald test).Each point shows the point estimate of HR from cox regression.Bars show 95%CI.(d) false discovery rate.The HR and 95%CI of metabolites (treated as continuous in model) were estimated using Cox regression with

Table S9 .
The sample size of study populations for each specific types of cancer risk are as follows: Nhead and neck cancer=161440; Nesophagus cancer=161401; Nstomach